Archives of Dermatological Research

, Volume 302, Issue 9, pp 669–677

A multi-component herbal preparation (PADMA 28) improves structure/function of corticosteroid-treated skin, leading to improved wound healing of subsequently induced abrasion wounds in rats

  • Muhammad Nadeem Aslam
  • Roscoe L. Warner
  • Narasimharao Bhagavathula
  • Isaac Ginsburg
  • James Varani
Original Paper

Abstract

PADMA 28 is a multi-component herbal mixture formulated according to an ancient Tibetan recipe. PADMA 28 is known to stimulate collagen production and reduced levels of collagen-degrading matrix metalloproteinases (MMPs). The goal of the present study was to determine whether topical treatment of rat skin with PADMA 28 would improve skin structure/function, and whether subsequently induced abrasion wounds would heal more rapidly in skin that had been pretreated with PADMA 28. Hairless rats were exposed to a potent topical corticosteroid (Temovate) in combination with either DMSO alone or with PADMA 28 given topically. At the end of the treatment period, superficial wounds were created in the skin, and time to wound closure was assessed. Collagen production and matrix-degrading MMPs were assessed. Abrasion wounds in skin that had been pretreated with PADMA 28 healed more rapidly than did wounds in Temovate plus DMSO-treated skin. Under conditions in which improved wound healing was observed, there was an increased collagen production and decreased MMP expression, but no significant epidermal hyperplasia and no evidence of skin irritation. The ability to stimulate collagen production and inhibit collagen-degrading enzymes in skin and facilitate more rapid wound closure without irritation should provide a rationale for development of the herbal preparation as a “skin-repair” agent.

Keywords

Type I collagen Matrix metalloproteinase Wound healing Skin repair PADMA 28 Temovate 

References

  1. 1.
    Anstead GM (1998) Steroids, retinoids, and wound healing. Adv Wound Care 11:277–285PubMedGoogle Scholar
  2. 2.
    Ashcroft GS, Mills SJ, Ashworth JJ (2002) Ageing and wound healing. Biogerontology 3:337–345CrossRefPubMedGoogle Scholar
  3. 3.
    Aslam MN, Fligiel H, Lateef H et al (2005) PADMA 28: a multi-component herbal preparation with retinoid-like dermal activity but without epidermal effects. J Invest Dermatol 124:524–529CrossRefPubMedGoogle Scholar
  4. 4.
    Drabaek H, Mehlsen J, Himmelstrup H et al (1993) A botanical compound, PADMA 28, increases walking distance in stable intermittent claudication. Angiology 44:863–867CrossRefPubMedGoogle Scholar
  5. 5.
    Elias PM, Fritsch P, Lampe M et al (1981) Retinoid effects on epidermal structure, differentiation and permeability. Lab Invest 44:531–540PubMedGoogle Scholar
  6. 6.
    Fisher GJ, Datta SC, Talwar HS et al (1996) Molecular basis of sun-induced premature skin ageing and retinoid antagonism. Nature 379:335–339CrossRefPubMedGoogle Scholar
  7. 7.
    Fisher GJ, Wang ZQ, Datta SC et al (1997) Pathophysiology of premature skin aging induced by ultraviolet light. New Engl J Med 337:1419–1428CrossRefPubMedGoogle Scholar
  8. 8.
    Fisher GJ, Kang S, Varani J et al (2002) Mechanisms of photoaging and chronological skin aging. Arch Dermatol 138:1462–1470CrossRefPubMedGoogle Scholar
  9. 9.
    Floyd EE, Jetten AM (1989) Regulation of type I (epidermal) transglutaminase mRNA levels during squamous differentiation: down-regulation by retinoids. Mol Cell Biol 9:4846–4851PubMedGoogle Scholar
  10. 10.
    Fry L (1988) Psoriasis. Br J Dermatol 119:445–461CrossRefPubMedGoogle Scholar
  11. 11.
    Griffiths CE, Russman AN, Majmudar G et al (1993) Restoration of collagen formation in photodamaged human skin by tretinoin (retinoic acid). New Engl J Med 329:530–535CrossRefPubMedGoogle Scholar
  12. 12.
    Griffiths CE, Kang S, Ellis CN et al (1995) Two concentrations of topical tretinoin (retinoic acid) cause similar improvement of photoaging but different degrees of irritation. A double-blind, vehicle-controlled comparison of 0.1% and 0.025% tretinoin creams. Arch Dermatol 131:1037–1044CrossRefPubMedGoogle Scholar
  13. 13.
    rGya mtsho sDS (1994) Gsoba rig pa’ bsten bcos smen bla’ dgongs rgyen rgyud bzhi’ gsal byed be dur snogpo’ mallika zhes bya bu bzhugs so—Smed cha. (Commentary to the rgyud bzhi, The Blue Beryll, vol II). Tibetan Medical & Astro Institute, DharamsalaGoogle Scholar
  14. 14.
    Jetten AM, George MA, Pettit GR et al (1989) Action of phorbol esters, bryostatins and retinoic acid on cholesterol sulfate synthesis: relation to the multistep process of differentiation in human epidermal keratinocytes. J Invest Dermatol 93:108–115CrossRefPubMedGoogle Scholar
  15. 15.
    Kang S, Duell EA, Fisher GJ et al (1995) Application of retinol to human skin in vivo induces epidermal hyperplasia and cellular retinoid-binding proteins characteristic of retinoic acid but without measurable retinoic acid levels or irritation. J Invest Dermatol 105:549–556CrossRefPubMedGoogle Scholar
  16. 16.
    Klenerman L, McCabe C, Cogley D et al (1996) Screening for patients at risk of diabetic foot ulceration in a general diabetic outpatient clinic. Diabet Med 13:561–563CrossRefPubMedGoogle Scholar
  17. 17.
    Kligman AM, Balin AK (1989) Aging of human skin. In: Balin AK, Kligman AM (eds) Aging and the human skin. Raven Press, New York, pp 1–11Google Scholar
  18. 18.
    Laing P (1998) The development and complications of diabetic foot ulcers. Am J Surg 176(2A Suppl):11S–19SCrossRefPubMedGoogle Scholar
  19. 19.
    Lateef H, Abatan OI, Aslam MN et al (2005) Topical pretreatment of diabetic rats with all-trans retinoic acid increases healing of subsequently induced abrasion wounds. Diabetes 54:855–861CrossRefPubMedGoogle Scholar
  20. 20.
    Lavker RM (1979) Structural alterations in exposed and unexposed aged skin. J Invest Dermatol 73:59–66CrossRefPubMedGoogle Scholar
  21. 21.
    Lavker RM (1995) Cutaneous aging: chronologic versus photoaging. In: Gilchrest BA (ed) Photoaging. Blackwell, Cambridge, MA, pp 123–135Google Scholar
  22. 22.
    Lovell CR, Smolenski KA, Duance VC et al (1987) Type I and III collagen content and fibre distribution in normal human skin during ageing. Br J Dermatol 117:419–428CrossRefPubMedGoogle Scholar
  23. 23.
    Margolis DJ, Allen-Taylor L, Hoffstad O et al (2002) Diabetic neuropathic foot ulcers: the association of wound size, wound duration, and wound grade on healing. Diabetes Care 25:1835–1839CrossRefPubMedGoogle Scholar
  24. 24.
    Margolis DJ, Kantor J, Berlin JA (1999) Healing of diabetic neuropathic foot ulcers receiving standard treatment. A meta-analysis. Diabetes Care 22:692–695CrossRefPubMedGoogle Scholar
  25. 25.
    McMichael AJ, Griffiths CE, Talwar HS et al (1996) Concurrent application of tretinoin (retinoic acid) partially protects against corticosteroid-induced epidermal atrophy. Br J Dermatol 135:60–64CrossRefPubMedGoogle Scholar
  26. 26.
    Melzer J, Brignoli R, Diehm C et al (2006) Treating intermittent claudication with Tibetan medicine Padma 28: does it work? Atherosclerosis 189:39–46CrossRefPubMedGoogle Scholar
  27. 27.
    Oikarinen A, Kallioinen M (1989) A biochemical and immunohistochemical study of collagen in sun-exposed and protected skin. Photodermatology 6:24–31PubMedGoogle Scholar
  28. 28.
    Phillips TJ, Gottlieb AB, Leyden JJ et al (2002) Efficacy of 0.1% tazarotene cream for the treatment of photodamage: a 12-month multicenter, randomized trial. Arch Dermatol 138:1486–1493CrossRefPubMedGoogle Scholar
  29. 29.
    Prakash A, Pandit PN, Sharman LK (1974) Studies in wound healing in experimental diabetes. Int Surg 59:25–28PubMedGoogle Scholar
  30. 30.
    Reiber GE (1996) The epidemiology of diabetic foot problems. Diabet Med 13:S6–S11PubMedGoogle Scholar
  31. 31.
    Sallon S, Beer G, Rosenfeld J et al (1998) The efficacy of PADMA 28, a herbal preparation, in the treatment of intermittent claudication: a controlled double-blind pilot study with objective assessment of chronic occlusive arterial disease patients. J Vasc Invest 4:129–136Google Scholar
  32. 32.
    Samochowiec L, Wojcicki J, Kosmider K et al (1987) Wirksamkeitsprüfung von PADMA 28 bei der Behandlung von Patienten mit chronischen arteriellen Durchblutungsstörungen. Herba Pol 33:29–41Google Scholar
  33. 33.
    Schräder R, Nachbur B, Mahler F (1985) Wirksamkeit von PADMA 28 auf die Claudicatio intermittens bei chronischer peripherer arterieller Verschlusskrankheit: Kontrollierte Doppelblindstudie. Schweiz Med Wochenschr 115:752–756PubMedGoogle Scholar
  34. 34.
    Schwartz E, Cruickshank FA, Christensen CC et al (1993) Collagen alterations in chronically sun-damaged human skin. Photochem Photobiol 58:841–844CrossRefPubMedGoogle Scholar
  35. 35.
    Schwartz E, Cruickshank FA, Perlish JS et al (1989) Alterations in dermal collagen in ultraviolet irradiated hairless mice. J Invest Dermatol 93:142–146CrossRefPubMedGoogle Scholar
  36. 36.
    Singer AJ, Clark RA (1999) Cutaneous wound healing. New Engl J Med 341:738–746CrossRefPubMedGoogle Scholar
  37. 37.
    Smith JG Jr, Davidson EA, Sams WM Jr et al (1962) Alterations in human dermal connective tissue with age and chronic sun damage. J Invest Dermatol 39:347–350CrossRefPubMedGoogle Scholar
  38. 38.
    Smulski HS, Wojcicki J (1995) Placebo controlled, double blind trial to determine the efficacy of the Tibetan plant preparation PADMA 28 for intermittent claudication. Altern Ther Health Med 1:44–49Google Scholar
  39. 39.
    Stadelmann WK, Digenis AG, Tobin GR (1998) Physiology and healing dynamics of chronic cutaneous wounds. Am J Surg 176(2A Suppl):26S–38SCrossRefPubMedGoogle Scholar
  40. 40.
    Strigini L, Ryan T (1996) Wound healing in elderly human skin. Clin Dermatol 14:197–206CrossRefPubMedGoogle Scholar
  41. 41.
    Varani J, Warner RL, Gharaee-Kermani M et al (2000) Vitamin A antagonizes decreased cell growth and elevated collagen-degrading matrix metalloproteinases and stimulates collagen accumulation in naturally aged human skin. J Invest Dermatol 114:480–486CrossRefPubMedGoogle Scholar
  42. 42.
    Varani J, Zeigler M, Dame MK et al (2001) Heparin-binding epidermal growth factor activation of keratinocyte ErbB receptors mediates epidermal hyperplasia, a prominent side-effect of retinoid therapy. J Invest Dermatol 117:1335–1341CrossRefPubMedGoogle Scholar
  43. 43.
    Varani J, Spearman D, Perone P et al (2001) Inhibition of type I procollagen synthesis by damaged collagen in photoaged skin and by collagenase-degraded collagen in vitro. Am J Pathol 158:931–942PubMedGoogle Scholar
  44. 44.
    Varani J, Schuger L, Dame MK et al (2004) Reduced fibroblast interaction with intact collagen as a mechanism for depressed collagen synthesis in photodamaged skin. J Invest Dermatol 122:1471–1479CrossRefPubMedGoogle Scholar
  45. 45.
    Varani J, Dame MK, Rittie L et al (2006) Decreased collagen production in chronologically aged skin: roles of age-dependent alteration in fibroblast function and defective mechanical stimulation. Am J Pathol 168:1861–1868CrossRefPubMedGoogle Scholar
  46. 46.
    Varani J, Perone P, O’Brien-Deming M et al (2009) Impaired keratinocyte function on matrix metalloproteinase-1 (MMP-1) damaged collagen. Arch Dermatol Res 301:497–506CrossRefPubMedGoogle Scholar
  47. 47.
    Warner RL, Bhagavathula N, Nerusu K et al (2008) MDI 301, a nonirritating retinoid, improves abrasion wound healing in damaged/atrophic skin. Wound Repair Regen 16:117–124CrossRefPubMedGoogle Scholar
  48. 48.
    Weiss JS, Ellis CN, Headington JT et al (1988) Topical tretinoin improves photoaged skin. A double-blind vehicle-controlled study. JAMA 259:527–532CrossRefPubMedGoogle Scholar
  49. 49.
    Wicke C, Halliday B, Allen D et al (2000) Effects of steroids and retinoids on wound healing. Arch Surg 135:1265–1270CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Muhammad Nadeem Aslam
    • 1
  • Roscoe L. Warner
    • 1
  • Narasimharao Bhagavathula
    • 1
  • Isaac Ginsburg
    • 2
  • James Varani
    • 1
  1. 1.Department of PathologyThe University of MichiganAnn ArborUSA
  2. 2.Institute of Dental Research, Faculty of Dental MedicineHadassah Medical Center, Hebrew UniversityJerusalemIsrael

Personalised recommendations